Histidine kinase domain profile

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use
phosphotransfer schemes involving two conserved components, a histidine
protein kinase (HK) and a response regulator protein (RR) (see <PDOC50110>).
The HK, which is regulated by environmental stimuli, autophosphorylates at a
histidine residue, creating a high-energy phosphoryl group that is
subsequently transferred to an aspartate residue in the RR domain.
Phosphorylation induces a conformational change in RR that results in
activation of an associated domain that effects the response.

Both prokaryotic and eukaryotic HKs contain the same basic signaling
components, namely a diverse sensing domain and a highly conserved kinase core
that has a unique fold, distinct from that of the Ser/Thr/Tyr kinase
superfamily. The overall activity of the kinase is modulated by input signals
to the sensing domain. HKs undergo an ATP-dependent autophosphorylation at a
conserved His residue in the kinase core. Autophosphorylation is a bimolecular
reaction between homodimers, in which one HK monomer catalyzes the
phosphorylation of the conserved His residue in the second monomer.

The sensing domains are variable in sequence, reflective of the many different
environmental signals to which HKs are responsive, whereas the about 250-residue kinase core is more conserved. The kinase core is composed of a
dimerization domain and an ATP/ADP-binding phosphotransfer or catalytic domain
and can be identified by five conserved primary sequence motifs present in
both eukaryotic and procaryotic HKs. These motifs have been termed the H, N,
G1, F and G2 boxes. The conserved His substrate is the central feature in the
H box, whereas the N, G1, F and G2 boxes define the nucleotide binding cleft.
In most HKs, the H box is part of the dimerization domain. However, for some
proteins, like CheA, the conserved His is located at the far N-terminus of the
protein in a separate HPt domain. The N, G1, F and G2 boxes are usually
contiguous, but the spacing between these motifs is somewhat varied. The
catalytic core forms an α-β sandwich consisting of five antiparallel
β strands and three α helices (see <PDB:1BXD>) [1,2,3].

The profile we developed covers the histidine kinase core.

Last update:

January 2002 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
Prosite License
or see: prosite_license.html.